Age-Stratified Prognostic Comparison of Three Chronotropic Incompetence Definitions in Patients with Suspected Coronary Artery Disease Undergoing Exercise Stress SPECT-MPI.

BACKGROUND

Chronotropic incompetence (CI) is an exercise-derived marker of impaired heart rate response with prognostic relevance in myocardial perfusion imaging, but its interpretation may vary by definition, particularly in older patients. We retrospectively compared three CI definitions in patients with suspected coronary artery disease undergoing symptom-limited exercise stress single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI).

METHODS

In this dual-center cohort, 1,135 patients undergoing exercise stress SPECT-MPI were evaluated. CI was defined as failure to achieve 85% of age-predicted maximal heart rate (CI-APMHR), heart rate reserve <80% (CI-HRR), or blunted heart rate reserve below a sex-specific lower limit of normal (CI-Blunted). The primary endpoint was major adverse cardiovascular events (MACE). Prevalence, agreement, multivariable Cox associations, incremental value beyond total perfusion deficit (TPD) and left ventricular ejection fraction (LVEF), age-stratified analyses, and age-by-CI interactions were assessed.

RESULTS

During a median follow-up of 63 months (IQR, 54-70), 144 patients (12.7%) experienced MACE. CI prevalence differed substantially across definitions: CI-HRR 83.9%, CI-Blunted 72.2%, and CI-APMHR 55.1% (all P < 0.001). Pairwise agreement was fair to moderate (κ range: 0.370-0.574). All three definitions were independently associated with MACE: CI-APMHR (HR 1.83; 95% CI: 1.25-2.69), CI-HRR (HR 2.92; 95% CI: 1.35-6.33), and CI-Blunted (HR 1.99; 95% CI: 1.21-3.28). Overall, all definitions added incremental prognostic value beyond TPD and LVEF. In patients aged ≥60 years, CI-APMHR showed the most consistent incremental performance. Age-by-CI interactions were not significant.

CONCLUSION

CI classification in exercise SPECT-MPI was definition-dependent. Although all three definitions were associated with MACE, their incremental prognostic performance beyond TPD and LVEF differed. In descriptive age-stratified analyses, CI-APMHR showed the most consistent incremental prognostic signal in patients aged ≥60 years. However, age-by-CI interactions were not statistically significant, supporting cautious, age-informed interpretation rather than definitive age-related effect modification.